Abstract:
OBJECTIVE:Niacin has been used for seven decades to modulate plasma lipids, but its mechanism of action is still unclear. We sought to determine whether variants in the niacin receptor gene, hydroxyl-carboxylic receptor 2 (HCAR2), are associated with lipid response to treatment. PARTICIPANTS AND METHODS:Coding variants, rs7314976 (p.R311C) and rs2454727 (p.M317I), were genotyped in 2067 participants from the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) trial. AIM-HIGH was a randomized, placebo-controlled trial that was conducted to assess the effect of extended-release niacin in patients with cardiovascular disease aggressively treated with low-density lipoprotein cholesterol-lowering therapy. RESULTS:There was no association of p.R311C or p.M317I with changes in low-density lipoprotein cholesterol, triglycerides, or high-density lipoprotein cholesterol at 1 year in groups receiving placebo or extended-release niacin. In White patients, the reduction in lipoprotein (a) [Lp(a)] in response to niacin was greater in homozygous carriers of the major 317M allele (-22.7%; P=0.005) compared with minor allele carriers (-15.3%). This was directionally consistent in the Black participants. Upon combining both groups, the reduction in Lp(a) in response to niacin was significantly greater in the homozygous major allele carriers (-23.0%; P=0.003) compared with minor allele carriers (-15.2%). CONCLUSION:Understanding the genetic contribution toward variation in response to niacin therapy, including Lp(a) reduction, could uncover mechanisms by which niacin decreases Lp(a), an important independent risk factor for cardiovascular disease.
journal_name
Pharmacogenet Genomicsjournal_title
Pharmacogenetics and genomicsauthors
Tuteja S,Wang L,Dunbar RL,Chen J,DerOhannessian S,Marcovina SM,Elam M,Lader E,Rader DJdoi
10.1097/FPC.0000000000000289subject
Has Abstractpub_date
2017-08-01 00:00:00pages
285-293issue
8eissn
1744-6872issn
1744-6880journal_volume
27pub_type
杂志文章,随机对照试验abstract::A possible association between the combination of genetic variations in hepatocyte nuclear factor 4α (HNF4α) and constitutive androstane receptor (CAR) and the stable doses of warfarin was examined in patients from the Ewha-Severance Treatment (EAST) Group of Warfarin. Around 42.5% of the overall interindividual varia...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000103
更新日期:2015-01-01 00:00:00
abstract:OBJECTIVE:Genome-wide single nucleotide polymorphism (SNP) association studies recently identified two SNPs (rs11833579 and rs12425791) on chromosome 12p13 that are associated with ischemic stroke (IS) in Caucasian or Black persons from America and the Netherlands. Our aim was to determine whether these SNPs were assoc...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32834911d0
更新日期:2011-09-01 00:00:00
abstract::We investigated the effect of the functional insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene on the response to interferon-β (IFN-β) therapy in Croatian and Slovenian patients with multiple sclerosis (MS). A total of 275 IFN-β treated MS patients [162 responders (Rs) and 113 nonre...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000283
更新日期:2017-06-01 00:00:00
abstract:OBJECTIVES:To determine whether functional polymorphisms of glutathione S-transferase μ type 1 (GSTM1) and aldehyde dehydrogenase-2 (ALDH2) affect the isosorbide 5-mononitrate (IS-5-MN) response, and the role of the calcitonin gene-related peptide (CGRP) in IS-5-MN response in healthy volunteers. METHODS:A two-phase, ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328343ea0a
更新日期:2011-03-01 00:00:00
abstract:INTRODUCTION:Efavirenz is primarily metabolized by CYP2B6, with a minor contribution from CYP1A2, CYP2A6, CYP3A4 and CYP3A5. Genetic variability in these genes contributes towards differences in plasma efavirenz concentration, which ultimately leads to either development of adverse drug events or emergence of virus res...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328363176f
更新日期:2013-08-01 00:00:00
abstract:RATIONALE:Selecting an effective treatment for patients with major depressive disorder is a perpetual problem for psychiatrists. It is of particular interest to explore the interaction between genetic predisposition and environmental factors. OBJECTIVES:Mouse inbred strains vary in baseline performance in depression-r...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32834b3f35
更新日期:2011-12-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to examine the associations between genetic variations in the human KCNK2 gene and major depressive disorder (MDD) and response to antidepressant treatment. METHOD:Four hundred and forty-nine patients with MDD and 421 normal controls were included in the study; among the MDD patient...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32832cbe61
更新日期:2009-10-01 00:00:00
abstract:OBJECTIVE:To investigate the utility of statistical tools in translating Affymetrix Drug Metabolizing Enzyme and Transporter (DMET) Assay single-nucleotide polymorphisms (SNPs) into common consensus star alleles. METHODS:DMET SNP data from clinical trials in different ethnicities were pooled for analyses. Three differ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000047
更新日期:2014-06-01 00:00:00
abstract:OBJECTIVES:Multiple sclerosis (MS) is a neurodegenerative chronic inflammatory. Mutations in the vitamin D receptor (VDR) gene can substantially affect serum vitamin D levels or alter its functionality, and can consequently increase susceptibility to developing MS. The objective of this study was to evaluate the associ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000420
更新日期:2021-02-01 00:00:00
abstract::We have identified the ATP-binding cassette (ABC) transporter ABCC4 as an active constituent of mediator-storing granules in human platelets. In addition to multidrug resistance protein 4, other ABC-type transport proteins may contribute to platelet secretory function as well as determine intended or adverse effects o...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32833997b0
更新日期:2010-06-01 00:00:00
abstract:OBJECTIVES:We have earlier shown that diet and xenobiotic metabolizing enzyme genotypes influence colorectal cancer risk, and now investigate whether similar associations are seen in patients with premalignant colorectal adenomas (CRA), recruited during the pilot phase of the Scottish Bowel Screening Programme. METHOD...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e3283395c6a
更新日期:2010-05-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Quetiapine is an atypical antipsychotic drug used to treat schizophrenia and acute episodes of mania. Quetiapine is metabolized by CYP3A enzymes including CYP3A5 and is a substrate of P-glycoprotein, an efflux drug transporter encoded by the ABCB1 gene. We assessed the effects of ABCB1 [c.1236...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000020
更新日期:2014-01-01 00:00:00
abstract:OBJECTIVES:We tested the effect of kidney-specific multidrug resistance-related protein (MRP2, ABCC2) deficiency on renal organic solute disposition as well as on renal protein and gene expression. Furthermore, we investigated whether a particular kidney donor ABCC2 genotype is associated with delayed graft function in...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328328d4e9
更新日期:2009-04-01 00:00:00
abstract:OBJECTIVE:To test the hypothesis that the two nonsynonymous single nucleotide polymorphisms at the CB2 cannabinoid receptor gene may have functional consequences on human CB2. METHODS:Q63R, H316Y, and Q63R/H316 mutations were made in recombinant human CB2 by the method of site-directed mutagenesis. After these mutant ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e3283367c6b
更新日期:2010-03-01 00:00:00
abstract::Lipid changes with statin treatments vary greatly between individuals for reasons which are largely unknown. This study was performed to examine the genetic determinants of lipid responses to rosuvastatin in Chinese patients. A total of 125 polymorphisms in 61 candidate genes from 386 Chinese patients were analyzed fo...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32833de489
更新日期:2010-10-01 00:00:00
abstract:OBJECTIVE:Substantial evidence indicates that nonsteroidal anti-inflammatory drugs protect against colorectal cancer by altering cell cycle progression and/or inducing apoptosis, whereas p53 protein is crucial to maintaining cell-cycle arrest and regulating DNA repair, differentiation, and apoptosis. Genetic variants i...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e3280d5121c
更新日期:2007-08-01 00:00:00
abstract:OBJECTIVES:To evaluate whether ABCC2 gene polymorphisms are associated with expression and/or function of the efflux pump. METHODS:We investigated the allele frequency of ABCC2 -24C>T, -23G>A, c.1249G>A, c.1446C>G, c.1457C>T, c.2302C>T, c.2366C>T, c.3542G>T, c.3561G>A, c.3563T>A, c.3972C>T, c.4348G>A, and 4544G>A in 3...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e3282f974b7
更新日期:2008-04-01 00:00:00
abstract:OBJECTIVES:Immediate reactions - particularly anaphylactic ones - to betalactams are the most common adverse reactions to antibiotics mediated by a specific immunologic mechanism. The genetic risk factors influencing these mechanisms are poorly known. We aimed to evaluate the association between immediate allergic reac...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000230409.00276.44
更新日期:2006-10-01 00:00:00
abstract:BACKGROUND:For prevention of joint destruction in rheumatoid arthritis, optimal management of therapy with disease-modifying antirheumatic drugs is essential. Pharmacogenomic evidence, if reliable, may be incorporated in the treatment of rheumatoid arthritis to achieve a more efficient activity control with minimized a...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000236326.80809.b1
更新日期:2007-06-01 00:00:00
abstract:BACKGROUND:HIV infection has been associated with dyslipidemia, insulin resistance, and changes in body composition, including loss of subcutaneous fat and skeletal muscle, with relative sparing of upper trunk and visceral fat. Because of its resemblance to Cushing's syndrome, caused by glucocorticoid excess, we hypoth...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000029
更新日期:2014-03-01 00:00:00
abstract:OBJECTIVES:To analyze whether gene variants leading to impaired drug metabolism are related with acute gastrointestinal bleeding after nonsteroidal anti-inflammatory drugs (NSAID) use. METHODS:Common CYP2C8 and CYP2C9 polymorphisms were studied in a cross-sectional study, involving 134 NSAID-related bleeding patients ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e3282f305a9
更新日期:2008-01-01 00:00:00
abstract::Clozapine is the drug of choice for treatment-resistant schizophrenia. However, its use is associated with variable clinical responses and serious adverse effects. Polymorphisms in genes encoding proteins involved in synaptic neurotransmission may account for such variability. Here, we studied independent and epistati...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000314
更新日期:2018-01-01 00:00:00
abstract:OBJECTIVE:Clinical response to antipsychotic medications can vary markedly in patients with schizophrenia. Identifying genetic variants associated with treatment response could help optimize patient care and outcome. To this end, we carried out a large-scale candidate gene study to identify genetic risk factors predict...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000122
更新日期:2015-04-01 00:00:00
abstract:BACKGROUND/AIM:Cytochrome P450 oxidoreductase (POR) is required for drug metabolism by all microsomal cytochrome P450 (CYP) enzymes. The aim of this study was to investigate whether single-nucleotide polymorphisms in the POR gene were correlated with interindividual variations in CYP2B6 activity, as measured by bupropi...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000190
更新日期:2016-02-01 00:00:00
abstract:BACKGROUND:5-Hydroxytryptamine 3 (5-HT3) receptors mediate the fast excitatory neurotransmission of serotonin. In this study, we have characterized the effects of four naturally occurring, nonsynonymous variants of the human 5-HT3B subunit on expression and signalling properties of heteromeric 5-HT3AB receptors. METHO...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328310f950
更新日期:2008-12-01 00:00:00
abstract::Endocrine disrupters, such as persistent organohalogen pollutants (POPs) may cause hypospadias, which is a common congenital anomaly in males, affecting 0.2-0.7%. We hypothesized that hypospadias incidence would be high among Greenlanders, who are one of the most POP exposed populations on earth through consumption of...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000199497.01101.93
更新日期:2006-05-01 00:00:00
abstract:OBJECTIVES:Prolonged activation of the β-1 adrenergic receptor (ADRB1) is associated with receptor desensitization. This process has been suggested to have important pathophysiological and clinical implications in conditions such as congestive heart failure. The contribution of genetic factors to this process is a subj...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000338
更新日期:2018-06-01 00:00:00
abstract::The human cytochrome P450 2A6 (CYP2A6) enzyme metabolizes several xenobiotic compounds of clinical or toxicological importance. We aimed to identify genetic variants and major CYP2A6 haplotypes associated with CYP2A6 phenotypic variation. CYP2A6 mRNA level, protein level, activity and haplotypes were determined in Cau...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000171517.22258.f1
更新日期:2005-09-01 00:00:00
abstract::Vitamin D has potent anti-tumour properties. Calcitriol [1,25(OH)2D3], the hormonal derivative of vitamin D3, is an antiproliferative and prodifferentiation factor for several cell types, including human squamous cells of the head and neck. Several polymorphisms of the vitamin D receptor (VDR) gene have been described...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01213011-200503000-00004
更新日期:2005-03-01 00:00:00
abstract:AIM/OBJECTIVES/BACKGROUND:Hypertension is a risk factor for cardiovascular and kidney disease and is most prevalent in African-American adults. The renin-angiotensin-aldosterone system is integral in blood pressure regulation; angiotensin-converting enzyme inhibitors such as ramipril are first-line treatment options. A...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,随机对照试验
doi:10.1097/FPC.0000000000000154
更新日期:2015-09-01 00:00:00